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Dapagliflozin modulates neuronal injury via instigation of LKB1/p-AMPK/GABA B R2 signaling pathway and suppression of the inflammatory cascade in an essential tremor rat model.
- Source :
-
Expert opinion on therapeutic targets [Expert Opin Ther Targets] 2023 Apr-May; Vol. 27 (4-5), pp. 373-392. Date of Electronic Publication: 2023 May 02. - Publication Year :
- 2023
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Abstract
- Background: However, disturbances in cellular energy demarcate neuronal hyperexcitability in essential tremor (ET); nevertheless, no available data relates energy sensors and GABAergic neurotransmission in ET. Noteworthy, reports have asserted dapagliflozin's (DAPA) role in enhancing autophagic sensors in other disorders. Herein, this study aims to investigate DAPA's impact on the GABA <subscript>B</subscript> receptor subunit (GABA <subscript>B</subscript> R2), notwithstanding the GABA A involvement, in an ET model.<br />Methods: ET was induced by a single dose of harmaline (30 mg/kg; i.p.), while DAPA (1 mg/kg/day; p.o.) was given for 5 days before ET induction. The autophagic sensors were examined by injecting a single dose of dorsomorphin (DORSO) AMPK inhibitor (0.2 mg/kg; i.p.) on the 5 <superscript>th</superscript> day before ET induction.<br />Results: DAPA decreased the HAR-induced tremor score and alleviated motor disabilities observed in the open field, rotarod, wire grip strength, and gait kinematics confirmed by reduced electrical activity in electroencephalogram. In the cerebella, DAPA curbed HAR-evoked inflammatory cytokines, apoptotic markers, and glutamate while restoring the disturbed GABA, BDNF, LKB1, p-AMPK, and GABA <subscript>B</subscript> R2 levels. DAPA's effect was mostly obliterated by DORSO.<br />Conclusion: DAPA offers a potential neuroprotective effect in ET by augmenting the neuronal inhibitory machinery via suppressing the inflammatory and excitotoxicity systems through LKB1/p-AMPK/GABA <subscript>B</subscript> R2 signaling.
Details
- Language :
- English
- ISSN :
- 1744-7631
- Volume :
- 27
- Issue :
- 4-5
- Database :
- MEDLINE
- Journal :
- Expert opinion on therapeutic targets
- Publication Type :
- Academic Journal
- Accession number :
- 37089040
- Full Text :
- https://doi.org/10.1080/14728222.2023.2206955